Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis

Harveen Dhillon, Jeffrey M. Zigman, Chianping Ye, Charlotte E. Lee, Robert A. McGovern, Vinsee Tang, Christopher D. Kenny, Lauryn M. Christiansen, Ryan D. White, Elisabeth A. Edelstein, Roberto Coppari, Nina Balthasar, Michael A. Cowley, Streamson Chua, Joel K. Elmquist, Bradford B. Lowell

Research output: Contribution to journalArticle

508 Scopus citations

Abstract

Leptin, an adipocyte-derived hormone, acts directly on the brain to control food intake and energy expenditure. An important question is the identity of first-order neurons initiating leptin's anti-obesity effects. A widely held view is that most, if not all, of leptin's effects are mediated by neurons located in the arcuate nucleus of the hypothalamus. However, leptin receptors (LEPRs) are expressed in other sites as well, including the ventromedial hypothalamus (VMH). The possible role of leptin acting in "nonarcuate" sites has largely been ignored. In the present study, we show that leptin depolarizes and increases the firing rate of steroidogenic factor-1 (SF1)-positive neurons in the VMH. We also show, by generating mice that lack LEPRs on SF1-positive neurons, that leptin action at this site plays an important role in reducing body weight and, of note, in resisting diet-induced obesity. These results reveal a critical role for leptin action on VMH neurons.

Original languageEnglish (US)
Pages (from-to)191-203
Number of pages13
JournalNeuron
Volume49
Issue number2
DOIs
StatePublished - Jan 19 2006

ASJC Scopus subject areas

  • Neuroscience(all)

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    Dhillon, H., Zigman, J. M., Ye, C., Lee, C. E., McGovern, R. A., Tang, V., Kenny, C. D., Christiansen, L. M., White, R. D., Edelstein, E. A., Coppari, R., Balthasar, N., Cowley, M. A., Chua, S., Elmquist, J. K., & Lowell, B. B. (2006). Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron, 49(2), 191-203. https://doi.org/10.1016/j.neuron.2005.12.021